keyword
MENU ▼
Read by QxMD icon Read
search

Population pk

keyword
https://www.readbyqxmd.com/read/29151114/non-canonical-heterogeneous-cellular-distribution-and-co-localization-of-camkii%C3%AE-and-camkii%C3%AE-in-the-spinal-superficial-dorsal-horn
#1
Max Larsson
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key enzyme in long-term plasticity in many neurons, including in the nociceptive circuitry of the spinal dorsal horn. However, although the role of CaMKII heterooligomers in neuronal plasticity is isoform-dependent, the distribution and co-localization of CaMKII isoforms in the dorsal horn have not been comprehensively investigated. Here, quantitative immunofluorescence analysis was used to examine the distribution of the two major neuronal CaMKII isoforms, α and β, in laminae I-III of the rat dorsal horn, with reference to inhibitory interneurons and neuronal populations defined by expression of parvalbumin, calretinin, and calbindin D28k...
November 18, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29149294/pharmacokinetics-pharmacodynamics-of-systemically-administered-polymyxin-b-against-klebsiella-pneumoniae-in-mouse-thigh-and-lung-infection-models
#2
Cornelia B Landersdorfer, Jiping Wang, Veronika Wirth, Ke Chen, Keith S Kaye, Brian T Tsuji, Jian Li, Roger L Nation
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29145924/pharmacokinetic-interaction-between-bedaquiline-and-clofazimine-in-patients-with-drug-resistant-tuberculosis
#3
G Maartens, M J E Brill, M Pandie, E M Svensson
<h2>BACKGROUND:</h2>Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ.<h2>METHODS:</h2>We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB...
November 16, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29144413/epstein-barr-virus-hijacks-dna-damage-response-transducers-to-orchestrate-its-life-cycle
#4
REVIEW
Pok Man Hau, Sai Wah Tsao
The Epstein-Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has shown that EBV triggers a DNA damage response (DDR) during primary infection and lytic reactivation. The EBV-encoded viral proteins have been implicated in deregulating the DDR signaling pathways...
November 16, 2017: Viruses
https://www.readbyqxmd.com/read/29136540/the-application-of-in-vitro-surveillance-data-for-antibacterial-dose-selection
#5
REVIEW
Robert K Flamm, Helio S Sader, Mariana Castanheira, Ronald N Jones
In vitro surveillance data, which provide key information to interpret the results of pharmacokinetic/pharmacodynamics (PK-PD) target attainment studies, are used to support dose selection decisions and recommendations for in vitro susceptibility testing criteria for antibacterial agents during drug development. Considerations for designing the in vitro surveillance database to support the development of antibacterial agents include the choice of pathogens to study, the sample size of isolate collections needed, and target patient populations from which clinical isolates should be collected...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#6
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29134648/pharmacokinetics-pharmacodynamics-and-proposed-dosing-of-the-oral-jak1-and-jak2-inhibitor-baricitinib-in-pediatric-and-young-adult-candle-and-savi-patients
#7
Hanna Kim, Kristina M Brooks, Cheng Cai Tang, Paul Wakim, Mary Blake, Stephen R Brooks, Gina A Montealegre Sanchez, Adriana A de Jesus, Yan Huang, Wanxia Li Tsai, Massimo Gadina, Apurva Prakash, Jonathan Marcus Janes, Xin Zhang, William L Macias, Parag Kumar, Raphaela Goldbach-Mansky
Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of the oral janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled in a compassionate use program. Patients received doses between 0.1 to 17 mg per day. Covariates of weight and renal function significantly influenced volume-of-distribution and clearance respectively. The half-life of baricitinib in patients less than 40kg was substantially shorter than in adult populations, requiring the need for dosing up to 4 times daily...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29134635/ribociclib-bioavailability-is-not-affected-by-gastric-ph-changes-or-food-intake-in-silico-and-clinical-evaluations
#8
Tanay S Samant, Shyeilla Dhuria, Yasong Lu, Marc Laisney, Shu Yang, Arnaud Grandeury, Martin Mueller-Zsigmondy, Kenichi Umehara, Felix Huth, Michelle Miller, Caroline Germa, Mohamed Elmeliegy
Ribociclib (KISQALI®), a cyclin-dependent kinase 4/6 inhibitor approved for the first-line treatment of HR+/HER2- advanced breast cancer with an aromatase inhibitor, is administered with no restrictions on concomitant gastric pH-elevating agents or food intake. The influence of proton pump inhibitors (PPIs) on ribociclib bioavailability was assessed using (1) biorelevant media solubility, (2) physiologically based pharmacokinetic (PBPK) modeling, (3) non-compartmental analysis (NCA) of clinical trial data, and (4) population PK (PopPK) analysis...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133566/use-of-pharmacokinetic-and-pharmacodynamic-analyses-to-determine-the-optimal-fixed-dosing-regimen-of-iclaprim-for-treatment-of-serious-gram-positive-infections
#9
Thomas Lodise, John Bosso, Colleen Kelly, Paul J Williams, James R Lane, David B Huang
Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two Phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection models studies suggest that the pharmacokinetic and pharmacodynamics (PK/PD) drivers for efficacy are area under the curve from 0-24 hours at steady state (AUC0-24hss), AUC/minimum inhibitory concentration (MIC), and time above the MIC during the dosing interval (T > MIC) while QTc prolongation was associated to maximal concentration at steady state (Cmaxss) in a thorough QTc Phase 1 study...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29133469/an-invisible-ubiquitin-conformation-is-required-for-efficient-phosphorylation-by-pink1
#10
Christina Gladkova, Alexander F Schubert, Jane L Wagstaff, Jonathan N Pruneda, Stefan M V Freund, David Komander
The Ser/Thr protein kinase PINK1 phosphorylates the well-folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We previously showed that Ser65 phosphorylation results in a conformational change in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation wherein the last β-strand is retracted to extend the Ser65 loop and shorten the C-terminal tail. We show using chemical exchange saturation transfer (CEST) nuclear magnetic resonance experiments that a similar, C-terminally retracted (Ub-CR) conformation also exists at low population in wild-type Ub...
November 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29133366/lifestyle-and-reproductive-factors-and-ovarian-cancer-risk-by-p53-and-mapk-expression
#11
Holly R Harris, Megan S Rice, Amy L Shafrir, Elizabeth M Poole, Mamta Gupta, Jonathan L Hecht, Kathryn L Terry, Shelley S Tworoger
BACKGROUND: One model of ovarian cancer development model divides tumors into two types. Type I tumors are characterized by KRAS and BRAF mutations, which can activate mitogen-activated protein kinase (MAPK). Type II tumors are characterized by tubal precursor lesions with p53 mutations. We evaluated the association between lifestyle and reproductive factors and risk of ovarian cancer defined by p53 and MAPK expression. METHODS: Epithelial ovarian cancer cases (n=274) and controls (n=1907) were identified from the Nurses' Health Study (NHS) and NHSII prospective cohorts, and the population-based New England Case-Control study...
November 13, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29130579/a-homozygous-deleterious-cdk10-mutation-in-a-patient-with-agenesis-of-corpus-callosum-retinopathy-and-deafness
#12
Vincent J Guen, Simon Edvardson, Nitay D Fraenkel, Aviva Fattal-Valevski, Chaim Jalas, Irene Anteby, Avraham Shaag, Talia Dor, David Gillis, Eitan Kerem, Jacqueline A Lees, Pierre Colas, Orly Elpeleg
The primary cilium is a key organelle in numerous physiological and developmental processes. Genetic defects in the formation of this non-motile structure, in its maintenance and function, underlie a wide array of ciliopathies in human, including craniofacial, brain and heart malformations, and retinal and hearing defects. We used exome sequencing to study the molecular basis of disease in an 11-year-old female patient who suffered from growth retardation, global developmental delay with absent speech acquisition, agenesis of corpus callosum and paucity of white matter, sensorineural deafness, retinitis pigmentosa, vertebral anomalies, patent ductus arteriosus, and facial dysmorphism reminiscent of STAR syndrome, a suspected ciliopathy...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29123025/mitogen-activated-protein-kinase-mapk-dynamics-determine-cell-fate-in-the-yeast-mating-response
#13
Yang Li, Julie Roberts, Zohreh AkhavanAghdam, Nan Hao
In the yeast Saccharomyces cerevisiae, the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29116330/identification-and-mapping-of-ts-tender-spines-a-gene-involved-in-soft-spine-development-in-cucumis-sativus
#14
Chunli Guo, Xuqin Yang, Yunli Wang, Jingtao Nie, Yi Yang, Jingxian Sun, Hui Du, Wenying Zhu, Jian Pan, Yue Chen, Duo Lv, Huanle He, Hongli Lian, Junsong Pan, Run Cai
Using map-based cloning of ts gene, we identified a new sort of gene involved in the initiation of multicellular tender spine in cucumber. The cucumber (Cucumis sativus L.) fruit contains spines on the surface, which is an extremely valuable quality trait affecting the selection of customers. In this study, we elaborated cucumber line NC072 with wild type (WT) hard fruit spines and its spontaneous mutant NC073, possessing tender and soft spines on fruits. The mutant trait was named as tender spines (ts), which is controlled by a single recessive nuclear gene...
November 7, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/29111469/an-in-silico-approach-to-determine-challenges-in-the-bioavailability-of-ciprofloxacin-a-poorly-soluble-weak-base-with-borderline-solubility-and-permeability-characteristics
#15
Simone Hansmann, Yoshihiro Miyaji, Jennifer Dressman
Ciprofloxacin is administered as the hydrochloride salt in immediate release formulations for the treatment of various infectious diseases in different patient populations. Due to its weakly basic properties and poor solubility, the in vivo behaviour of this compound could be influenced by both physicochemical and physiological factors. The first aim of this study was to investigate the behaviour of ciprofloxacin (Ciprobay® 500 mg tablets) in the human gastro-intestinal tract with in vitro dissolution, transfer and two-stage experiments...
October 27, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29107547/camkii%C3%AE-expression-defines-two-functionally-distinct-populations-of-granule-cells-involved-in-different-types-of-odor-behavior
#16
Sarah Malvaut, Simona Gribaudo, Delphine Hardy, Linda Suzanne David, Laura Daroles, Simon Labrecque, Marie-Anne Lebel-Cormier, Zayna Chaker, Daniel Coté, Paul De Koninck, Martin Holzenberger, Alain Trembleau, Isabelle Caille, Armen Saghatelyan
Granule cells (GCs) in the olfactory bulb (OB) play an important role in odor information processing. Although they have been classified into various neurochemical subtypes, the functional roles of these subtypes remain unknown. We used in vivo two-photon Ca(2+) imaging combined with cell-type-specific identification of GCs in the mouse OB to examine whether functionally distinct GC subtypes exist in the bulbar network. We showed that half of GCs express Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα(+)) and that these neurons are preferentially activated by olfactory stimulation...
November 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29106979/development-of-a-population-pharmacokinetic-model-to-predict-brain-distribution-and-dopamine-d2-receptor-occupancy-of-raclopride-in-non-anesthetized-rat
#17
Yin Cheong Wong, Trayana Ilkova, Rob C van Wijk, Robin Hartman, Elizabeth C M de Lange
BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to occupy the available D2 receptors and antagonize the action of dopamine or drugs on D2 in preclinical studies. The aims of this study were to comprehensively evaluate its pharmacokinetic (PK) profiles in different brain compartments and to establish a PK-RO model that could predict the brain distribution and RO of raclopride in the freely moving rat using a LC-MS based approach...
November 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29100789/the-rice-cold-responsive-calcium-dependent-protein-kinase-oscpk17-is-regulated-by-alternative-splicing-and-post-translational-modifications
#18
M Cecília Almadanim, Nuno M Gonçalves, Margarida T G Rosa, Bruno M Alexandre, André M Cordeiro, Mafalda Rodrigues, Nelson J M Saibo, Cláudio M Soares, Célia V Romão, M Margarida Oliveira, Isabel A Abreu
Plant calcium-dependent protein kinases (CDPKs) are key proteins implicated in calcium-mediated signaling pathways of a wide range of biological events in the organism. The action of each particular CDPK is strictly regulated by many mechanisms in order to ensure an accurate signal translation and the activation of the adequate response processes. In this work, we investigated the regulation of a CDPK involved in rice cold stress response, OsCPK17, to better understand its mode of action. We identified two new alternative splicing (AS) mRNA forms of OsCPK17 encoding truncated versions of the protein, missing the CDPK activation domain...
October 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29100425/promoter-methylation-of-tumor-related-genes-as-a-potential-biomarker-using-blood-samples-for-gastric-cancer-detection
#19
Jinfeng Wen, Tuo Zheng, Kefeng Hu, Chunxia Zhu, Lihua Guo, Guoliang Ye
Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A (p16), E-cadherin (CDH1), runt-related transcription factor 3 (RUNX3), human mutL homolog 1 (MLH1), RAS association domain family protein 1A (RASSF1A), cyclin-dependent kinase inhibitor 2B (p15), adenomatous polyposis coli (APC), Glutathione S-transferase P1 (GSTP1), TP53 dependent G2 arrest mediator candidate (Reprimo), and O6-methylguanine-DNAmethyl-transferase (MGMT) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29084032/dosopt-a-tool-for-personalized-bayesian-dose-adjustment-of-vancomycin-in-neonates
#20
Tõnis Tasa, Tuuli Metsvaht, Riste Kalamees, Jaak Vilo, Irja Lutsar
BACKGROUND: Our main aim has been to design a framework to improve vancomycin dosing in neonates. This required the development and verification of a computerized dose adjustment application, DosOpt, to guide the selection. METHODS: Model fitting in DosOpt uses Bayesian methods for deriving individual pharmacokinetic (PK) estimates from population priors and patient therapeutic drug monitoring measurements. These are used to simulate concentration-time curves and target-constrained dose optimization...
December 2017: Therapeutic Drug Monitoring
keyword
keyword
57095
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"